Necrotic bone conditions, such as idiopathic or secondary osteonecrosis, avascular bone necrosis, glucocorticoid induced bone ischemia/osteonecrosis, Legg-Calve-Perthes disease and femoral head necrosis are severe debilitating conditions. These conditions can be associated with medical interventions such as high dose glucocorticoid therapy and various treatments for HIV/AIDS, or they can arise spontaneously in susceptible individuals or as a consequence of other diseases such as Cushing syndrome, Storage diseases (i.e. Gauchers disease), haemaglobinopathies (e.g. sickle cell disease), pancreatitis, dysbaric conditions or trauma (e.g. dislocation or fracture).
Osteonecrosis is characterized by distinct histopathological features apparent on radiographs or bone scans. Although diagnostic methods for its identification have improved in recent years with the introduction of new sensitive high resolution MRI and other imaging techniques, no effective therapeutic agents or medical interventions have yet been developed to prevent and/or treat this condition.
Several pathological situations can induce osteonecrotic conditions, but among the most common clinical situations are high dose glucocorticoid use and treatments with apoptosis inducing compounds, such as the high dose anti-retroviral treatments administered to HIV infected patients.
Although most skeletal sites can be affected by osteonecrosis, the condition is most commonly found in the bone of the femoral head underneath the articular surface of the hip joint. The medical intervention of choice remains orthopedic surgery, where the necrotic bone area and affected joint structures are removed and replaced with a suitable implant. In some patients with necrotic bone disease, such as juveniles or patients with severe medical conditions, it can be highly problematic to perform this type of orthopedic surgery, and thus there is an unmet medical need for new medical therapies for prophylaxis and/or treatment of necrotic bone disease.